Affinage

RANBP10

Ran-binding protein 10 · UniProt Q6VN20

Length
620 aa
Mass
67.3 kDa
Annotated
2026-06-10
23 papers in source corpus 16 papers cited in narrative 16 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 6/6 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

RANBP10 is a cytoplasmic multidomain scaffold protein that links Ran nucleotide exchange, microtubule regulation, and CTLH E3 ubiquitin ligase assembly across hematopoietic, neuronal, and proliferative contexts (PMID:18347012, PMID:19801445, PMID:40883813). It functions as a guanine nucleotide exchange factor for Ran through a discrete GEF domain whose activity is abolished by a single point mutation, and it binds β-tubulin to control non-centrosomal microtubule organization (PMID:18347012). In megakaryocytes and platelets this microtubule role is physiologically essential: loss of RANBP10 in mice distorts platelet discoid shape, disrupts microtubule filament number and localization, prolongs bleeding time, and impairs granule release and stable thrombus formation, in part by failing to restrain premature β1-tubulin polymerization (PMID:19801445, PMID:22936655). RANBP10 is an integral subunit of the CTLH/GID E3 ubiquitin ligase complex, where it can independently nucleate complex assembly through CRA-domain interface features and acts as a partial antagonist of its paralog RANBP9, tuning ubiquitylation output and cell proliferation such that a higher RANBP9/RANBP10 ratio favors growth (PMID:36459484, PMID:40883813, PMID:41948802). Through its IUS-SPRY β-sandwich domain it engages partner peptides at a defined shallow binding surface and competes with RANBP9 for receptor tyrosine kinase MET binding without activating downstream Ras/Erk signaling (PMID:14684163, PMID:27622290). RANBP10 additionally co-activates the androgen and glucocorticoid receptors via direct complex formation (PMID:18222118), suppresses FBXW7 promoter activity to stabilize c-Myc in glioblastoma (PMID:34671019), modulates D1 dopamine receptor phosphorylation through PKC (PMID:20395553), and participates in HPV16 nuclear import by forming a transport complex with KPNA2 and DYNLT3 (PMID:33974675).

Mechanistic history

Synthesis pass · year-by-year structured walk · 13 steps
  1. 2004 Medium

    Established that RANBP10, unlike its paralog RanBPM/RANBP9, binds the MET kinase domain via its SPRY domain but is a signaling-inert competitor that cannot couple to Sos or activate Ras/Erk, defining functional divergence within the Scorpin family.

    Evidence Co-IP, binding competition, and SRE-luciferase reporter assays in cell lines

    PMID:14684163

    Open questions at the time
    • Physiological consequence of MET competition not shown in vivo
    • Did not define which signaling outputs RANBP10 does control at MET
  2. 2005 Medium

    An ortholog screen implicated the RANBP10 family in negatively regulating JAK/STAT signaling by controlling nucleocytoplasmic transport of STAT, hinting at a transport-scaffolding role.

    Evidence Genome-wide dsRNA RNAi screen in Drosophila cells with STAT92E phosphorylation readout

    PMID:16055650

    Open questions at the time
    • Drosophila homolog, not human RANBP10
    • Direct molecular mechanism of STAT transport control not resolved
  3. 2008 High

    Defined RANBP10's core biochemical identity as a cytoplasmic Ran-GEF that also binds β-tubulin and organizes microtubules, unifying nucleotide exchange and cytoskeletal functions.

    Evidence In vitro GEF assay with GEF-domain point mutant, β-tubulin co-IP, and RNAi in megakaryocytes

    PMID:18347012

    Open questions at the time
    • How Ran-GEF activity relates mechanistically to tubulin binding unclear
    • Substrate/spatial regulation of the GEF activity not mapped
  4. 2008 Medium

    Showed RANBP10 acts as a nuclear-receptor coactivator, enhancing androgen and glucocorticoid (but not estrogen) receptor transactivation and forming homo- and hetero-oligomers with RANBP9, extending its scaffold role into transcriptional control.

    Evidence Luciferase reporter assays, co-IP, and co-localization microscopy

    PMID:18222118

    Open questions at the time
    • Direct vs indirect interaction with AR not distinguished
    • Mechanism of coactivation (chromatin, transport) unresolved
  5. 2009 High

    Demonstrated in vivo that RANBP10 is required for platelet discoid shape, microtubule organization, hemostasis, and degranulation, validating the cytoskeletal function physiologically.

    Evidence Gene-trap knockout mouse with ultrastructure, flow cytometry, and bleeding time assays

    PMID:19801445

    Open questions at the time
    • Did not separate GEF activity from tubulin binding for the phenotype
    • Molecular basis of granule release defect not defined
  6. 2010 Medium

    Connected RANBP10 to GPCR signaling, showing it complexes with PKCγ/δ and the D1 dopamine receptor and promotes PKC-dependent receptor phosphorylation that attenuates cAMP signaling.

    Evidence Co-IP/mass spectrometry, immunofluorescence, cAMP and phosphorylation assays with PKC inhibitors

    PMID:20395553

    Open questions at the time
    • Whether RANBP10 is a direct PKC substrate-presenting scaffold not established
    • In vivo relevance in neurons not tested
  7. 2012 High

    Refined the platelet phenotype mechanistically, showing RANBP10 loss raises β1-tubulin and drives premature microtubule polymerization that blocks agonist-induced marginal band contraction and stable thrombus formation.

    Evidence RANBP10-null mouse with ferric chloride thrombosis, flow adhesion, aggregometry, β1-tubulin Western, and taxol phenocopy

    PMID:22936655

    Open questions at the time
    • How RANBP10 represses β1-tubulin levels mechanistically unclear
    • Link between Ran-GEF activity and tubulin homeostasis untested
  8. 2016 High

    Provided the structural basis for partner recognition, defining the RANBP10 IUS-SPRY β-sandwich fold and its shallow conserved binding surface that engages partner peptides with micromolar affinity.

    Evidence X-ray crystallography, KD measurement, and interface mutagenesis

    PMID:27622290

    Open questions at the time
    • Endogenous SPRY-domain ligands beyond the test peptide not catalogued
    • Structure of GEF and CRA domains not solved here
  9. 2017 Medium

    Implicated RANBP10 dosage in neurodegeneration, showing miR-196a suppresses RANBP10 and that excess RANBP10 reduces β-tubulin polymerization and worsens neuronal morphology and transport in a Huntington's disease model.

    Evidence 3'UTR luciferase reporter, miRNA and RANBP10 dosage manipulation, neuronal morphology/transport assays in HD mice

    PMID:28744327

    Open questions at the time
    • Direct molecular target of RANBP10 in neurons not identified
    • Causal contribution to human HD not established
  10. 2021 Medium

    Expanded RANBP10's scaffold roles to viral nuclear import and oncogenic signaling, showing it forms a KPNA2/DYNLT3 transport complex for HPV16 nuclear entry and suppresses FBXW7 to stabilize c-Myc in glioblastoma.

    Evidence Mass spectrometry, co-IP, microscopy, virological assays (HPV16); promoter-luciferase and FBXW7-silencing epistasis with proliferation/invasion assays (GBM)

    PMID:33974675 PMID:34671019

    Open questions at the time
    • Whether RANBP10's CTLH/E3 or GEF activity drives these effects unknown
    • Mechanism of FBXW7 promoter suppression undefined
  11. 2022 Medium

    Placed RANBP10 within the CTLH E3 ubiquitin ligase as a stage-specific subunit during erythropoiesis, with CTLH inactivation impairing erythroid maturation and enucleation.

    Evidence Quantitative proteomics of human erythropoiesis and CRISPR-Cas9 knockout with maturation/enucleation assays

    PMID:36459484

    Open questions at the time
    • RANBP10-specific effects not fully separated from RANBP9
    • Ubiquitylation substrates in erythropoiesis not defined
  12. 2025 Medium

    Established RANBP10 as an independent CTLH-assembly subunit and partial antagonist of RANBP9 whose overexpression reshapes the ubiquitylome to lower proliferation-associated and DNA replication factors, tying complex stoichiometry to growth control.

    Evidence Inducible cell lines, quantitative proteomics, ubiquitylome profiling, and proliferation assays in NSCLC

    PMID:40883813

    Open questions at the time
    • Direct ubiquitylation substrates not definitively assigned to RANBP10
    • Molecular basis of RANBP9 antagonism not structurally resolved
  13. 2026 Medium

    Defined the structural code for RANBP10's incorporation into the GID/CTLH ring, showing CRA-domain interface features encode its assembly specificity, which can be reprogrammed by targeted mutagenesis.

    Evidence X-ray crystallography of CTLH-CRA domains with quantitative binding and pairing-reprogramming mutagenesis

    PMID:41948802

    Open questions at the time
    • Full CTLH ring architecture with RanBP10 not resolved
    • Functional consequence of reprogrammed pairing in cells not tested

Open questions

Synthesis pass · forward-looking unresolved questions
  • It remains unresolved how RANBP10's distinct biochemical activities — Ran-GEF, β-tubulin/microtubule regulation, SPRY-mediated partner binding, and CTLH E3 ligase assembly — are integrated or differentially deployed across its many cellular contexts.
  • No study dissects which domain activity drives each phenotype
  • Endogenous ubiquitylation substrates of RANBP10-CTLH unidentified
  • Relationship between GEF activity and tubulin regulation untested

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0008092 cytoskeletal protein binding 2 GO:0060090 molecular adaptor activity 2 GO:0098772 molecular function regulator activity 1 GO:0140110 transcription regulator activity 1
Localization
GO:0005829 cytosol 2 GO:0005856 cytoskeleton 2 GO:0005634 nucleus 1
Pathway
R-HSA-109582 Hemostasis 2 R-HSA-162582 Signal Transduction 2 R-HSA-392499 Metabolism of proteins 2
Partners
ARDYNLT3KPNA2METPRKCGRANBP9TUBBYPEL5
Complex memberships
CTLH/GID E3 ubiquitin ligase complexKPNA2-DYNLT3 HPV16 nuclear import complex

Evidence

Reading pass · 16 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2004 RanBP10 interacts with the tyrosine kinase domain of MET via its SPRY domain, competing with RanBPM/RanBP9 for MET binding. Unlike RanBPM/RanBP9, RanBP10 fails to interact with Sos and cannot activate the Ras/Erk pathway; co-transfection of RanBP10 with RanBPM/RanBP9 represses RanBPM-induced SRE-luciferase reporter activity. Co-immunoprecipitation, binding competition assays, SRE-luciferase reporter gene assay, overexpression in cell lines Biochemical and biophysical research communications Medium 14684163
2005 Drosophila homolog of RanBP10 acts as a negative regulator of JAK/STAT signaling by controlling nucleocytoplasmic transport of STAT92E, identified in a genome-wide RNAi screen. Genome-wide dsRNA-mediated RNAi screen in cultured Drosophila cells, STAT92E phosphorylation assay Genes & development Medium 16055650
2008 RanBP10 is a cytoplasmic guanine nucleotide exchange factor (GEF) for Ran; it binds beta-tubulin and associates with megakaryocyte microtubules. A point mutation in the candidate GEF domain abolishes exchange activity. RNAi-mediated loss of RanBP10 in cultured megakaryocytes disrupts microtubule organization. In vitro GEF activity assay, point mutagenesis of GEF domain, beta-tubulin co-immunoprecipitation, RNAi knockdown with microtubule organization readout The Journal of biological chemistry High 18347012
2008 RanBP10 acts as a coactivator of the androgen receptor (AR): it enhances ligand-dependent AR transcriptional activity, forms a complex with AR, and shows additive effects with RanBPM on AR transactivation. RanBP10 also enhances glucocorticoid receptor but not estrogen receptor alpha transcriptional activity. RanBP10 forms homo-oligomers and hetero-oligomers with RanBPM and co-localizes with RanBPM in cytoplasm and nucleus. Luciferase reporter transcriptional assay, co-immunoprecipitation, co-localization by fluorescence microscopy Biochemical and biophysical research communications Medium 18222118
2009 RanBP10-deficient mice (gene-trap) show altered platelet shape (increased geometric axis ratio), disorders in microtubule filament numbers and localization in platelets, markedly prolonged bleeding time, and reduced platelet granule release (reduced CD62P and CD63 surface expression after PAR4 stimulation), establishing that RanBP10 is required for platelet discoid shape and degranulation in vivo. Gene-trap mouse knockout, ultrastructural analysis, flow cytometry, bleeding time assay, proplatelet formation assay Blood High 19801445
2010 RanBP10 interacts with PKCgamma and PKCdelta (identified by co-immunoprecipitation coupled to mass spectrometry) and with the D1 dopamine receptor. Overexpression of RanBP10 enhances basal D1 receptor phosphorylation and attenuates D1 receptor-stimulated cAMP accumulation; PKC inhibitors block the RanBP10-dependent increase in receptor phosphorylation. Co-immunoprecipitation coupled to mass spectrometry, co-localization by immunofluorescence, cAMP accumulation assay, receptor phosphorylation assay, PKC inhibitor treatment Molecular pharmacology Medium 20395553
2010 YPEL5 protein binds RanBP10 (and RanBPM) as identified by yeast two-hybrid, defining RanBP10 as part of a conserved Scorpin protein family alongside RanBPM. Yeast two-hybrid, comparative genomic analysis Genomics Low 20580816
2012 RanBP10-null platelets show normal adhesion on collagen and von Willebrand factor under flow but impaired stable thrombus formation in vivo (ferric chloride model). Loss of RanBP10 leads to increased β1-tubulin protein driving α-monomers into polymerized microtubules; agonists fail to contract the peripheral marginal band or centralize granules in null platelets. Taxol-induced microtubule stabilization in wild-type platelets phenocopies the attenuated shape change, supporting RanBP10's role in inhibiting premature β1-tubulin polymerization. RanBP10-null mouse model, ferric chloride arterial thrombosis model, flow adhesion assay, aggregometry, Western blot for β1-tubulin, taxol pharmacological phenocopy Blood High 22936655
2016 Crystal structures of the IUS-SPRY domain of RanBP10 (and RanBPM) were determined, revealing a β-sandwich fold with conserved loops forming a shallow binding surface including two aspartates, a positive patch, and a tryptophan. The DDX-4 peptide (residues 228–247) binds this surface with a KD of ~13 μM; mutagenesis studies defined the interaction interface. X-ray crystallography, binding affinity measurement (KD), mutagenesis Journal of molecular biology High 27622290
2017 miR-196a suppresses RANBP10 expression by binding its 3' UTR; higher RANBP10 expression impairs neuronal morphology, reduces β-tubulin polymerization, and worsens pathological aggregates in Huntington's disease model. Overexpression of RANBP10 exacerbates neuronal morphology deficits and intracellular transport impairment. 3' UTR luciferase reporter assay, miRNA overexpression, RANBP10 overexpression/knockdown, neuronal morphology and transport assays in HD transgenic mouse model Theranostics Medium 28744327
2021 RanBP10 forms a protein complex with karyopherin alpha2 (KPNA2) and dynein light chain DYNLT3 to facilitate HPV16 L2/vDNA transport towards mitotic chromatin during viral nuclear import, identified by label-free mass spectrometry and validated by biochemical and virological assays. Label-free mass spectrometry, biochemical co-immunoprecipitation, microscopy, functional virological infection assays PLoS pathogens Medium 33974675
2021 RANBP10 was identified as an IDO2-binding protein (but not IDO1-binding) in a co-immunoprecipitation screen, implicating it as a potential mediator of IDO2's nonenzymatic proinflammatory function in autoimmune arthritis. Co-immunoprecipitation Journal of immunology Low 34965962
2021 RANBP10 suppresses the promoter activity of FBXW7, thereby increasing c-Myc protein stability in glioblastoma cells. Silencing FBXW7 in RANBP10-knockdown GBM cells partially rescues the proliferation/migration/invasion defects caused by RANBP10 loss, placing RANBP10 upstream of the FBXW7–c-Myc axis. Promoter-luciferase reporter assay, RANBP10 knockdown/overexpression, epistasis rescue by FBXW7 silencing, proliferation and invasion assays Cell death & disease Medium 34671019
2022 During human erythropoiesis, RANBP10 and RANBP9 form maturation stage-dependent distinct CTLH E3 ubiquitin ligase complexes; CRISPR-Cas9 inactivation of CTLH E3 assemblies (including RANBP10-containing complexes) causes defects in erythroid maturation, spontaneous/accelerated erythroid differentiation, and inefficient enucleation. Quantitative proteomics of in vitro human erythropoiesis, CRISPR-Cas9 knockout, enucleation and maturation assays eLife Medium 36459484
2025 RANBP9 and RANBP10 (Scorpins) can each independently support formation of the CTLH E3 ubiquitin ligase complex and act as partial antagonists: acute overexpression of RANBP10 slows NSCLC cell proliferation and reshapes the cellular proteome and ubiquitylome, decreasing levels of proliferation-associated proteins including key DNA replication factors. A higher RANBP9/RANBP10 ratio correlates with greater proliferation. Inducible overexpression/loss-of-function cell lines, quantitative proteomics, ubiquitylome profiling, cell proliferation assays Journal of experimental & clinical cancer research Medium 40883813
2026 Crystal structures of CTLH-CRA domains of multiple CTLH complex subunits were determined; targeted perturbations of conserved CRA-CRA interface features allow engineered RanBP10 subunits to adopt non-native interaction partners, demonstrating that RanBP10's assembly specificity within the GID/CTLH E3 ligase ring is encoded by specific sequence and geometric features of its CRA domain. X-ray crystallography of CTLH-CRA domains, quantitative binding analyses, mutagenesis to reprogram pairing eLife Medium 41948802

Source papers

Stage 0 corpus · 23 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2005 Genome-wide RNAi analysis of JAK/STAT signaling components in Drosophila. Genes & development 193 16055650
2009 Ran on tracks--cytoplasmic roles for a nuclear regulator. Journal of cell science 74 19225125
2010 YPEL5 protein of the YPEL gene family is involved in the cell cycle progression by interacting with two distinct proteins RanBPM and RanBP10. Genomics 58 20580816
2008 RanBP10 is a cytoplasmic guanine nucleotide exchange factor that modulates noncentrosomal microtubules. The Journal of biological chemistry 47 18347012
2005 The SPRY domain-containing SOCS box protein 1 (SSB-1) interacts with MET and enhances the hepatocyte growth factor-induced Erk-Elk-1-serum response element pathway. The Journal of biological chemistry 46 15713673
2017 miR-196a Enhances Neuronal Morphology through Suppressing RANBP10 to Provide Neuroprotection in Huntington's Disease. Theranostics 44 28744327
2019 The CTLH Complex in Cancer Cell Plasticity. Journal of oncology 43 31885576
2015 MiR-378 Plays an Important Role in the Differentiation of Bovine Preadipocytes. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 39 26159460
2005 Gene profiling involved in immature CD4+ T lymphocyte responsible for systemic lupus erythematosus. Molecular immunology 39 16143398
2004 A novel MET-interacting protein shares high sequence similarity with RanBPM, but fails to stimulate MET-induced Ras/Erk signaling. Biochemical and biophysical research communications 38 14684163
2009 The microtubule modulator RanBP10 plays a critical role in regulation of platelet discoid shape and degranulation. Blood 33 19801445
2010 Identification of RanBP 9/10 as interacting partners for protein kinase C (PKC) gamma/delta and the D1 dopamine receptor: regulation of PKC-mediated receptor phosphorylation. Molecular pharmacology 29 20395553
2008 RanBP10 acts as a novel coactivator for the androgen receptor. Biochemical and biophysical research communications 26 18222118
2022 Modular UBE2H-CTLH E2-E3 complexes regulate erythroid maturation. eLife 25 36459484
2021 The Immunomodulatory Enzyme IDO2 Mediates Autoimmune Arthritis through a Nonenzymatic Mechanism. Journal of immunology (Baltimore, Md. : 1950) 22 34965962
2021 A Ran-binding protein facilitates nuclear import of human papillomavirus type 16. PLoS pathogens 18 33974675
2021 RANBP10 promotes glioblastoma progression by regulating the FBXW7/c-Myc pathway. Cell death & disease 16 34671019
2012 Altered microtubule equilibrium and impaired thrombus stability in mice lacking RanBP10. Blood 16 22936655
2018 Scorpins in the DNA Damage Response. International journal of molecular sciences 11 29914204
2016 Structural Basis for the Interaction between the IUS-SPRY Domain of RanBPM and DDX-4 in Germ Cell Development. Journal of molecular biology 11 27622290
2020 RANBP9 as potential therapeutic target in non-small cell lung cancer. Journal of cancer metastasis and treatment 4 34778565
2025 RANBP9 and RANBP10 cooperate in regulating non-small cell lung cancer proliferation. Journal of experimental & clinical cancer research : CR 2 40883813
2026 A structural code for assembly specificity in GID/CTLH-type E3 ligases. eLife 0 41948802

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